Matrix protein composition for dentin regeneration
View Patent ↗The present invention relates to the surprising finding that enamel matrix, enamel matrix derivatives and/or enamel matrix proteins induce dentin regeneration. The invention thus relates to the use of a preparation of an active enamel substance for the preparation of a pharmaceutical composition for the formation or regeneration of dentin following dental procedures involving exposure of vital dental pulp tissue. In another aspect, the invention relates to a method of promoting the formation or regeneration of dentin following dental procedures involving exposure of vital dental pulp tissue, the method comprising applying an effective amount of an active enamel substance on exposed vital dental pulp tissue after dental procedures.
1. A method of promoting one or more of regeneration of secondary dentin, formation of reparative dentin, or formation of osteodentin in a mammal, the method comprising administering to exposed vital dental pulp tissue of said mammal an active enamel substance comprising enamel matrix proteins selected from the group including one or more of enamelins, amelogenins, amelins, ameloblastin, sheathlin, tuftelins, dentinsialoprotein, and dentinsialophosphoprotein in an amount sufficient to promote one or more of regeneration of secondary dentin or formation of reparative dentin or formation of osteodentin.
2. The method of claim 1 , wherein the step of administering the active enamel substance comprises causing the active enamel substance to contact the mammal's vital dental pulp tissue.
3. The method according to claim 1 , wherein said vital dental pulp tissue is comprised in erupted teeth.
4. The method according to claim 1 , wherein the mammal is human.
5. The method according to claim 4 , wherein the human is older than about 12 years old.
6. The method of claim 1 , further comprising the step of applying a filling material to the exposed vital dental pulp of said mammal following a dental procedure involving exposure of the mammal's vital dental pulp tissue.
7. The method according to claim 1 , wherein the active enamel substance is of porcine origin.
8. The method according to claim 1 , wherein the active enamel substance is of synthetic origin.
9. The method according to claim 1 , wherein the active enamel substance is an enamel matrix or an enamel matrix protein.
10. The method according to claim 1 , wherein the active enamel substance comprises at least two substances selected from the group consisting of amelogenins, enamelins, amelins, ameloblastin, sheathlin, tuftelins, tuft proteins, serum proteins, salivary proteins, dentinsialoprotein, and dentinsialophosphoprotein.
11. The method according to claim 1 , wherein the active enamel substance comprises amelogenins.
12. The method according to claim 1 , wherein the active enamel substance has a molecular weight of at most about 120 kDa, as determined by SDS electrophoresis.
13. The method according to claim 1 , wherein the active enamel substance has a molecular weight of at most about 100 kDa, as determined by SDS electrophoresis.
14. The method according to claim 1 , wherein the active enamel substance has a molecular weight of at most about 90 kDa, as determined by SDS electrophoresis.
15. The method according to claim 1 , wherein the active enamel substance has a molecular weight of at most about 80 kDa, as determined by SDS electrophoresis.
16. The method according to claim 1 , wherein the active enamel substance has a molecular weight of at most about 70 kDa, as determined by SDS electrophoresis.
17. The method according to claim 1 , wherein the active enamel substance has a molecular weight of at most about 60 kDa, as determined by SDS electrophoresis.
18. The method according to claim 1 , wherein the active enamel substance has a molecular weight below about 60 kDa, as determined by SDS electrophoresis.
19. The method according to claim 1 , wherein the active enamel substance has a molecular weight up to about 40 kDa, as determined by SDS electrophoresis.
20. The method according to claim 1 , wherein the active enamel substance has a molecular weight between 5 kDa and 25 kDa, as determined by SDS electrophoresis.
21. The method according to claim 1 , wherein the active enamel substance has a molecular weight of about 25 kDa, as determined by SDS electrophoresis.
22. The method according to claim 1 , wherein the active enamel substance has a molecular weight of about 20 kDa, as determined by SDS electrophoresis.
23. The method according to claim 1 , wherein the active enamel substance has a molecular weight of about 5 kDa, as determined by SDS electrophoresis.
24. The method according to claim 1 , wherein the active enamel substance comprises a mixture of active enamel substances having different molecular weights.
25. The method according to claim 1 , wherein the active enamel substance includes one or more of amelogenin, amelin, tuftelin and dentinsialoprotein having a molecular weight below about 60 kDa, as determined by SDS electrophoresis.
26. The method according to claim 1 , wherein at least a part of the active enamel substance is in the form of aggregates or after application in viva is capable of forming aggregates.
27. The method according to claim 26 , wherein the aggregates have a molecular weight from about 5 kDa to about 40 kDa, as determined by SDS electrophoresis.
28. The method according to claim 26 , wherein the aggregates have a particle size from about 20 nm to about 1 μm.
29. The method according to claim 1 , wherein a pharmaceutical composition comprising the active enamel substance is administered to the mammal.
30. The method according to claim 29 , wherein the pharmaceutical composition comprises a pharmaceutically acceptable excipient.
31. The method according to claim 30 , wherein the pharmaceutically acceptable excipient is propylene glycol alginate.
32. The method according to claim 29 , wherein the pharmaceutical composition comprises about 30 mg/ml active enamel substance in propylene glycol alginate.
33. The method according to claim 1 , wherein the amount of active enamel substance applied to the mammal's vital dental pulp tissue is an amount of total protein per mm 2 of dental pulp tissue corresponding to from 0.005 mg/mm 2 to 5.0 mg/mm 2 .
34. The method according to claim 33 , wherein the amount of active enamel substance applied to the mammal's vital dental pulp tissue is an amount of total protein per mm 2 of dental pulp tissue corresponding to from 0.01 mg/mm 2 to 3.0 mg/mm 2 .
35. The method according to claim 1 , wherein the active enamel substance is applied at a concentration between 0.01 mg/ml to 40 mg/ml.
36. The method according to claim 1 , wherein the active enamel substance is applied at a concentration between 0.1 mg/ml to 30 mg/ml.
37. The method according to claim 1 , wherein the active enamel substance has a protein content from about 0.05% w/w to 100% w/w.